POS1265 DISTURBED CELLULAR IMMUNITY FOLLOWING mRNA VACCINATION AGAINST COVID-19 IN PATIENTS WITH B-CELL DEPLETING THERAPY
Authors: C. Sallegger, I. Hodl, B. Dreo, V. L. Ihm, J. Thiel, M. Stradner, J. Fessler, C. Consortium
Journal: Annals of the Rheumatic Diseases (2022)

Background Immunocompromised patients are considered high-risk and prioritized for vaccination against COVID-19 (1). Furthermore, vaccination-induced CD4 and CD8 T-cell responses have been suggested to have a protective role in COVID-19 (2). If T-cell responses are diminished after vaccination in immunocompromised individuals is not known to date. Objectives To investigate cellular immunity following mRNA vaccination against COVID-19 in healthy individuals and patients undergoing B-cell depletion therapy. Methods In this interim analysis of the CoVVac study ( NCT04858607 ), we analyzed T-cell responses in autoimmune patients treated with B-cell depleting therapy (BD, n=41) and age-matched healthy controls (HCs, n=50) 3-4 weeks after the second dose of mRNA vaccination against COVID-19. Therefore, we isolated PBMCs and stimulated them with a peptide pool covering the spike protein in vitro . Reactive CD4 and CD8 T-cells were determined by staining for IFNg, TNFa, IL-2 and GzmB by flow cytometry. Anti-SARS-CoV-2 antibody assays targeting the receptor-binding domain (RBD) or trimeric S protein (TSP) were performed to elucidate concomitant B-cell responses. Results We observed significant alterations in anti-SARS-CoV-2 antibody responses in our cohort, the frequency of IFNg+ and IL-2+ CD4 and CD8 T-cells was similar in BD patients and controls. On the other hand, TNFa+ CD4 T-cells were significantly enriched in healthy controls versus BD patients (p=0.017) and correlated significantly with antibody titres (p=0.003). Similarly, GzmB+ CD8 T-cells were significantly diminished in our patient cohort (p&lt;0.001) and also showed a significant correlation with antibody titres (p&lt;0.001). Overall, the frequency of GzmB+ CD8 T-cells correlated very well with reactivity of T-cell subsets for other cytokines. This effect, however, is lost in the BD cohort. No difference was observed in the frequency of TNFa+ CD8 T-cells between the groups. Only 21 (42%) healthy individuals and 14 (34%) patients showed reactive T-cells for all the cytokines tested. This observation is mainly explained by a lack of cytokine production of CD8 T-cells in 26 (52%) HCs and 27 (66%) BD patients. In turn, 22 (44%) HCs and 17 (42%) patients didn’t show any IL-2 producing CD8 cells. Of note, only 2 (4%) of HCs showed no GzmB+ CD8 T-cells whereas the number increased to 15 (37%) of BD individuals (p&lt;0.001). In contrast, 42 (84%) HCs as well as 32 (78%) of patients showed production of all IFNg, TNFa and IL-2 in CD4 T-cells. Conclusion Our data suggest that most patients with B-cell depleting therapy are able to mount T-cell responses similar to those of healthy individuals while a minority of these patients did not show complete immunity against SARS CoV-2. Further analyses are needed to better understand a possible link of B-cell depletion therapy and CD8 T-cell responses. References [1]Shields AM, Burns SO, Savic S, Richter AG; UK PIN COVID-19 Consortium. COVID-19 in patients with primary and secondary immunodeficiency: The United Kingdom experience. J Allergy Clin Immunol. 2021 Mar;147(3):870-875.e1. [2]Angyal, A., Longet, S., Chalk, J., 2022. T-cell and antibody responses to first BNT162b2 vaccine dose in previously infected and SARS-CoV-2-naive UK health-care workers: a multicentre prospective cohort study. The Lancet Microbe 3 Disclosure of Interests None declared